Intensified ocean exploration has revealed that high pressure causes severe and disabling nervous system disturbances in divers working at great depths (High Pressure Nervous Syndrom, HPNS). General anesthetics and lipid soluble inert gases antagonize the effects of pressure and thus can ameliorate the symptoms of HPNS. The antagonism between hyperbaric pressure and anesthetic agents is mutual; high pressure antagonizes anesthesia produced by a variety of anesthetic agents. The basis for anesthesia, HPNS, and for the mutal antagonism between pressure and anesthetic agents is not known. The proposed study is designed to test the hypothesis that pressure relief of anesthetic conduction block is due to opposing effects of anesthetics and pressure on the membrane rate constants which govern sodium channel inactivation. Further studies will clarify the basis for anesthetic inhibition of pressure-induced axon hyperexcitability. Finally, studies will be carried out to test the hypothesis that clinical concentrations of anesthetics and modest pressures can significantly modify axon properties, and thus to show whether or not axon membrane may be important in understanding anesthesia and HPNS. The bulk of the studies will be carried out on the node of Ranvier of vertebrate myelinated nerve, under both voltage-clamp and current clamp conditions. Additional studies will employ extra- and intra-cellular recording, including sucrose gap recording, on invertebrate branching axons and mammalian nonmyelinated sympathetic trunk axons.